Chronic excessive alcohol consumption depletes brain stores of omega-3 fatty acids which are necessary for optimal neural function. In our ongoing clinical trial of aggressive alcoholics, we determine if treatment with 2.8 g/d of omega-3 fatty acids will reduce 1) aggressive behaviors, 2) improve neurochemical measures of serotonergic function as well as other neurotransmitters associate with impulsivity and alcohol use 3) reduce measures of craving 4) reduce risk of relapse. This protocol is active and has enrolled 96 subjects with 100% tracking of data. Preliminary results indicate that anger is reduced by 33% (p<0.0008) in 12 weeks. An unexpected finding was the substantial reduction of heavy drinking days among recovering alcoholics. Those compliant with the protocol in the active group drank 3.2 days/90 while those ocompliant in the placebo group drank 17 days/ 90. This indicates tha treatment with omega-3 fatty acids may have an effect size of 8.4. In comparison the effect size of Naltrexone, also used for relapse prevention , has an effect size of 0.2. Greater omega-3 fattty acid plasma status on admission correlated with less brain atrophy indicating that these fatty may protect from alcohol induced brain atrophy. The study has completed enrollemnt and is under analysis. These findings complement a placebo controlled clinical trial conducted with collaboration with Laure-Budens Branchey, M.D., among polysubstance dependent subjects where omega-3 fatty acids reduced anger scores by 50% over 4 months. In a collaborative trial among subjects admitted to an emergency room with deliberate self harm, we found that 2 g/d of omega-3 fatty acids reduced future suicidal thinking, anger and depression scores while improving positive outlooks to life. Extending these findings to normative populations, we found that lower plasma levels of omega-3 fatty acids correlated with greater neuroticism and less agreeableness among healthy controls. In an observational trial conduced with Dr. Muldoon at the University of Pittsburgh. These data indicate that deficiencies impair affect in otherwise normal populations. Mothers can become depleted of omega-3 essential fatty acids during pregnancy when their dietary intake is inadequate. Dietary deficiencies may increase the risk of depressive symptoms for the mothers. Preliminary data is available from an open trial of omega-3 fatty acids among women with depression during pregnancy currently being conducted in collaboration with Marlene Freeman, MD at the University of Arizona. Depressive symptoms were reduced an average of 43.5 % during 8 weeks of treatment. These findings are significant as they offer a treatment for depression during pregnancy that is not only non-toxic, but has additional health benefits to pregnant women and their babies. These findings are being followed up with a randomized, controlled trial which has enrolled n=60 subjects. The results of these interventional trials were predicted from data from an epidemiological study of the dietary intake of omega-3 fatty acids during pregnancy among nearly 14,500 women enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). Findings were robust after rigorous examination of potential confounding factors. In a prior publication we found that the 2004 FDA and EPA advisory for women to limit seafood consumption during pregnancy inadvertently creates neurodevelopmental harm to the children. The children of mothers who ate seafood below the limit advised had greater risks of peer problems, poor prosocial behaviors and low verbal IQ and poorer performance on British nationally administered standardized academic tests. The work was conducted in collaboration with the ALSPAC study and examined nearly 9,000 children. These data have formed the core of an FDA model that reevaluates both the risks and benefts of seafood consumption in pregnancy, issued 15 JAN 2009. These data can be evaluated to determine if inadequate intake during pregnancy or early childhood is a risk factor for future substance abuse. We have collaborated with Marc Schuckit, M.D and Jean Golding, Ph.D. in designing a study to prospectively capture initial drinking behavior of these children as they enter adolescence. If this is identified as a risk factor, prevention studies can be planned. Dietary intakes that meet criteria for Recommended Daily Intakes (RDAs) have been calculated from two sources of data: cross-national data sets and the ALSPAC cohort study. Dose response relationships were derived comparing greater intake of seafood and lower prevalence rates of four psychiatric disorders and lower mortality rates of eight major causes. These publications are the only calculations of DRI's for long chain omega-3 fatty acids that utilize the Institute of Medicine statistical methodologies. In order to further refine this finding we utilized the observation that the omega-6 fatty acids from seed oils compete for inclusion in tissues with omega-3 fatty acids, which are rich in seafood. The amount of omega-3 fatty acids required to reduce risk of illness can be reduced 10-fold by consuming fewer omega-6 fatty acids from seed oils. In a developing collaboration with the Department of Defence, we are evaluating if restoring adequate omega-3 fatty acid nutritional status can reduce or prevent neuropsychiatric harm among military personnel.